Comparative Effectiveness of Field-Treatments for Multiple Actinic

描述（由申请人提供）：非黑色素瘤皮肤癌（NMSC）是美国最常见的癌症，每年诊断超过200万例。尽管受影响的人口众多，并由此产生的疾病负担，没有有效的化学预防策略已被确定，特别是在太阳受损的个人与现有的癌前皮肤病变谁是在发展皮肤癌的高风险。光化性角化病（AK）是癌前皮肤病变，出现在阳光损伤的皮肤上，并可进展为NMSC。用于治疗多种AK的两种最广泛使用的局部药剂是5-氟尿嘧啶（5-FU）和咪喹莫特。尽管在美国，AK的就诊量每年超过370万次，并且其治疗对我们的医疗保健系统造成了巨大的经济负担，每年花费超过10亿美元，但没有研究比较这些两种局部基于场的疗法的有效性。我们建议使用Kaiser Permanente北方加州（KPNC）的回顾性数据，比较5-FU和咪喹莫特在预防NMSC（主要目的）和AK（次要目的）方面的有效性。我们还试图确定每种药物在5年随访期内的剂量反应曲线。该项目的独特之处之一是设置，它允许在现实世界的实践环境中确定有效性。KPNC还提供了丰富的电子数据库的额外优势，具有丰富的暴露信息（详细的药房数据库），结果（识别无需报告的皮肤癌的独特NMSC登记）和潜在相关的协变量。该提案的另一个独特之处在于回顾性观察数据的处理方式，利用新的生物统计学方法（点治疗边际结构模型）得出关于暴露与结局之间关系的因果推断，如在临床试验环境中获得的那样。这些新开发的方法以前尚未用于皮肤流行病学。该项目的目标与NIAMS的长期规划目标相一致，即通过执行“皮肤病治疗的治疗方法和联合治疗方法的比较有效性”来增加皮肤相关的临床研究。“通过实现我们的研究目标，我们可以帮助确定高危人群中最有效的局部药物，以预防美国最常见的癌症。

DESCRIPTION (provided by applicant): Non-melanoma skin cancer (NMSCs) is the most common cancer in America, with over 2 million cases diagnosed annually. Despite the large population affected and resultant burden of disease, no effective chemopreventative strategies have been identified, especially among sun-damaged individuals with existing precancerous skin lesions who are at high risk of developing skin cancer. Actinic keratoses (AKs) are precancerous skin lesions that arise on sun-damaged skin and can progress to NMSCs. The two most widely used topical agents for the treatment of multiple AKs are 5- fluorouracil (5-FU) and imiquimod. Although visits for AKs accounts for over 3.7 million ambulatory care office visits per year in the US and their treatment poses a substantial financial burden to our healthcare system, costing over a billion dollars annually, no studies have compared the effectiveness of the these twp topical field-based therapies. We propose to compare the effectiveness of 5-FU and imiquimod in preventing NMSCs (primary aim) and AKs (secondary aim) using retrospective data from Kaiser Permanente Northern California (KPNC). We also seek to ascertain dose-response curves for each drug over a 5 year follow-up period. One of the unique features of the project is the setting, which allows for ascertainment of effectiveness in a real-world practice environment. KPNC also offers the added advantage of rich electronic databases, with a wealth of information of exposure (detailed pharmacy database), outcome (unique NMSC registry which identified non-reportable skin cancer), and potentially relevant co-variates. The other unique aspect of this proposal is the way in which the retrospective observational data is approached, utilizing novel biostatistical methodologies (point-treatment marginal structural models) to draw casual inference regarding the relationship between exposure and outcome as would be obtained in a clinical trial setting. These newly developed methods have not been previously used in Dermato-epidemiology. The goals of this project align with NIAMS's long-range planning goals of increasing skin related clinical research by performing "comparative effectiveness of therapies, and combination therapy approaches for skin disease treatment." By accomplishing our study aims, we can help identify the most effective topical agent among high risk individuals for the prevention of the most common cancer in America.